The purpose of the proposed studies is to define precisely the processes involved in iron uptake, utilization or storage, and eventually release by cells in key tissues throughout the body. Emphasis will be placed on studies of physiologic systems and iron compounds normally present in health or disease. Attention will be directed initially to iron metabolism by isolated rat liver cells, the placenta, and the Fletcher-Huehns phenomenon of selective release of iron from the two binding sites on transferrin. Liver cells isolated by the use of chelates, enzymes or mechanical means will be used to measure binding of radioiron from rat transferrin with determination of the number and avidity of iron binding sites, competition by other metals and proteins, the formation of intracellular ferritin, and the release of iron under various stresses to iron metabolism. Transferrin-bound radioiron uptake by placental structures of pregnant rats will be analyzed to identify placenta iron receptor sites and small molecular weight carrier substances involved in this unidirectional iron transfer. Functional heterogeneity of iron atoms on transferrin will be explored in vivo to determine whether selective release of iron to erythroid precursors, liver cells, placenta and other tissues occurs.